The goal of the studies dexcribed in this proposal is to develop gene transfer methods for the treatment of some human genetic diseases, with special reference to their application to the Lesch-Nyhan disease. We shall study the mechanisms of transfer of the HPRT gene and several other model genes by retroviral vectors into human and other mammalian cells in vitro and into whole mice by bone marrow repopulation and by systemic infection. Using optimally effecient retroviral vectors lacking all viral genes and other regulatory sequences thought to be harmful for recipient cells, we shall introduce the HPRT vector into patients with the Lesch-Nyhan disease, and determine if there is evidence in the patients of amelioration of the chemical or neurological aspects of the disorder.